Spirapril

MECHANISM OF ACTION

Spirapril inhibits angiotensin-converting enzyme (ACE), blocking the conversion of angiotensin I to angiotensin II within the renin-angiotensin-aldosterone system (RAAS). This leads to vasodilation, reduced blood pressure, and decreased aldosterone secretion. As a prodrug, spirapril is converted in the body to its active form, spiraprilat, which exerts the ACE-inhibiting effect.

PHARMACOKINETICS

Absorption

Spirapril is well absorbed after oral administration, with a bioavailability of approximately 50%. The drug is then extensively converted to its active metabolite, spiraprilat, primarily in the liver. 

Distribution

Spirapril has a relatively large volume of distribution, indicating extensive tissue penetration. Reported values for the volume of distribution of its active metabolite, spiraprilat, range from approximately 0.8 to 1.5 L/kg, depending on the study and species evaluated.

Metabolism

Spirapril undergoes extensive hepatic metabolism, where it is converted to its active metabolite, spiraprilat. This biotransformation primarily occurs through ester hydrolysis in the liver. Spiraprilat is responsible for the drug’s pharmacological activity as an ACE inhibitor, and it has a longer half-life than the parent compound, contributing to spirapril’s once-daily dosing efficacy.

Excretion

Spirapril is eliminated via both renal and hepatic pathways, allowing safer use in patients with kidney impairment compared to ACE inhibitors cleared mainly by the kidneys. Its active metabolite, spiraprilat, has an elimination half-life of approximately 40 hours.

PHARMACODYNAMICS

Spirapril is a prodrug converted to its active form, spiraprilat, which inhibits ACE and blocks the conversion of angiotensin I to angiotensin II. This results in vasodilation, lowered blood pressure, and reduced aldosterone secretion, promoting sodium and water excretion.

ADMINISTRATION

Spirapril is administered orally, typically once daily, with or without food. Its long duration of action allows for convenient dosing, and dosage adjustments may be required in patients with severe hepatic or renal impairment.

DOSAGE AND STRENGTH

• Spirapril is available in tablet form, commonly in strengths of 3 mg, 6 mg, and 12 mg.

• The usual starting dose for hypertension in adults is 3 mg once daily, which may be increased to 6–12 mg once daily depending on the patient’s response and clinical condition.

• Dose adjustments may be necessary for individuals with renal or hepatic impairment.

DRUG INTERACTIONS

Spirapril, an ACE inhibitor, may interact with various medications, including NSAIDs (e.g., ibuprofen), which can raise the risk of kidney issues; potassium supplements and potassium-sparing diuretics, which may cause elevated potassium levels; and antidepressants or other antihypertensive drugs, which can alter blood pressure effects. It can also interact seriously with lithium and sacubitril. Therefore, it’s important to inform your doctor about all medications you’re taking before starting spirapril.

FOOD INTERACTIONS

When taking spirapril, patients should limit high-potassium foods (e.g., bananas, oranges, potatoes) and reduce salt intake. Certain herbal supplements like ephedra and licorice should be avoided. Additionally, similar to other ACE inhibitors such as captopril, spirapril may be better absorbed on an empty stomach.

CONTRAINDICATIONS

Spirapril is contraindicated in pregnancy and breastfeeding, in patients with a history of angioedema from prior ACE inhibitor use, and in those with severe renal impairment. It should also be avoided in cases of severe hyperkalemia or anuria, and combining it with certain drugs, such as potassium-sparing diuretics, may increase the risk of adverse effects.

SIDE EFFECTS

Common side effects:

• Dry cough.

• Dizziness.

• Fatigue.

• Headache.

• Hyperkalemia.

Serious side effects: 

• Angioedema.

• Kidney dysfunction.

• Severe allergic reaction.

• Hypotension (low blood pressure).

OVERDOSE

• Dizziness or lightheadedness, especially when standing up.

• Extreme fatigue or unusual weakness.

• Confusion.

• Rapid or slow heartbeat (palpitations).

• Nausea.

• Blurred vision.

• Cold, clammy, pale skin.

• Rapid, shallow breathing.

• Acute renal failure (kidney injury) in severe cases.

• Hyperkalemia (high potassium levels in the blood). 

TOXICITY

Spirapril toxicity may cause serious effects such as angioedema, kidney dysfunction, and allergic reactions. It can also lead to hyperkalemia, particularly when combined with certain medications, and can be harmful to a fetus if used during pregnancy. Patients should promptly report any adverse symptoms, including dry cough, dizziness, or signs of infection, to their healthcare provider.